Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas.
Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas.
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DOI：
10.3892/ijo.2015.3191
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发表时间：
2015-12
影响因子：
5.2
通讯作者：
Kyo S
中科院分区：
文献类型：
--
作者：
Katagiri H;Nakayama K;Razia S;Nakamura K;Sato E;Ishibashi T;Ishikawa M;Iida K;Ishikawa N;Otsuki Y;Nakayama S;Kyo S
本研究的目的是阐明自噬在OCCC顺铂（CDDP）敏感性中的作用以及Beclin 1在OCCC进展中的作用。使用以下测量自噬：i）LC 3和p62的蛋白质印迹分析和ii）GFP-LC 3斑点的显微镜观察。使用氯喹和Beclin 1 siRNA抑制自噬。用免疫组化法检测手术标本中Beclin 1蛋白的表达。探讨Beclin 1表达缺失与临床病理特征、预后及化疗敏感性的关系。通过氯喹或Beclin 1 siRNA抑制自噬并没有增强ES 2和TOV-21 G OCCC细胞系对CDDP的敏感性。在38.3%（23/60）的分析肿瘤中观察到Beclin 1表达缺失。Beclin 1表达缺失与FIGO分期、CA 125水平、患者年龄、子宫内膜异位症状态、Ki-67标记指数、化疗方案或残留肿瘤状态无显著相关性。然而，在接受细胞减灭术，随后接受标准铂类化疗方案的OCCC中，与Beclin 1阳性表达相比，Beclin 1阴性表达与较短的无进展生存期相关（P=0.027，对数秩检验）。Beclin 1阴性肿瘤与Beclin 1阳性肿瘤相比，对主要辅助化疗的耐药性并不高（50.0% vs. 66.7%，P=0.937）。在ES 2和TOV-21 G OCCC细胞系中，使用siRNA敲低Beclin 1增加细胞生长，但不增加细胞迁移和侵袭。Beclin 1缺失导致的自噬缺陷与卵巢癌的化疗耐药和转移无关，但可能与卵巢癌的恶性表型和预后不良有关。
The aim of the present study was to clarify the role of autophagy in cisplatin (CDDP) sensitivity in OCCCs and the role of Beclin 1 in OCCC progression. Autophagy was measured using: i) western blot analysis of LC3 and p62 and ii) microscopic observation of GFP-LC3 puncta. Autophagy was suppressed using chloroquine and Beclin 1 siRNA. Surgical specimens were examined for Beclin 1 protein expression by immunohistochemistry. The correlations between the loss of Beclin 1 expression and clinicopathological characteristics, prognosis and chemosensitivity were investigated. Inhibition of autophagy by chloroquine or Beclin 1 siRNA did not enhance the sensitivity of the ES2 and TOV-21G OCCC cell lines to CDDP. Loss of Beclin 1 expression was observed in 38.3% (23/60) of the analyzed tumors. There was no significant correlation between loss of Beclin 1 expression and FIGO stage, CA125 levels, patient age, status of endometriosis, Ki-67 labeling index, chemotherapy regimen or status of residual tumor. However, negative expression of Beclin 1 was associated with a shorter progression-free survival in comparison to positive Beclin 1 expression in OCCC who received cytoreductive surgery, followed by a standard platinum-based chemotherapy regimen (P=0.027, log-rank test). Beclin 1-negative tumors were no more resistant to primary adjuvant chemotherapy than were Beclin 1-positive tumors (50.0 vs. 66.7%, P=0.937). Beclin 1 knockdown using siRNA increased cell growth but not cell migration and invasion in ES2 and TOV-21G OCCC cell lines. Autophagy defects caused by loss of Beclin 1 are not related to chemoresistance and metastasis, but may be associated with malignant phenotype and poor prognosis of OCCC.